Improvement effects and mechanism of sinomenine on non-alcoholic steatohepatitis in mice
- VernacularTitle:青藤碱对小鼠非酒精性脂肪性肝炎的改善作用及机制
- Author:
Cheng ZENG
1
,
2
;
Liangkun WENG
2
Author Information
1. Key Specialty of Clinical Pharmacy，the First Affiliated Hospital of Guangdong Pharmaceutical University，Guangzhou 510699，China
2. Center for Drug Research and Development，Guangdong Pharmaceutical University，Guangzhou 510006，China
- Publication Type:Journal Article
- Keywords:
non-alcoholic steatohepatitis;
sinomenine;
AMPK;
YAP;
inflammatory reaction
- From:
China Pharmacy
2024;35(14):1701-1707
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the improvement effects of sinomenine （Sin） on non-alcoholic steatohepatitis （NASH） and its potential mechanism. METHODS Male C57BL/6J mice were randomly divided into standard chow diet （SCD） group， high- fat diet （HFD） group， Sin low-dose group （Sin-L group， 50 mg/kg）， and Sin high-dose group （Sin-H group， 100 mg/kg）， with 6 mice in each group. The mice of SCD groups were fed with SCD， and other groups were given HFD for consecutive 24 weeks to establish NASH model. Since 17th week， the mice in each drug group were given corresponding drug solutions intragastrically， once a day， for 8 consecutive weeks. After the last medication， the body weight and liver weight of mice were determined， and liver indexes were calculated. The contents of total cholesterol （TC） and triglyceride （TG） in liver tissue， the serum contents of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， interleukin-1β （IL-1β） and IL-18 were all determined. Hepatic steatosis and fibrosis were observed， and hepatic lipid droplets were located. The expressions of IL-18 and IL-1β mRNA， inflammation-related proteins （IL-1β， cleaved-IL-1β）， fibrosis-related proteins [collagen Ⅰ （Col-Ⅰ）， α-smooth muscle actin （α-SMA）， connective tissue growth factor （CTGF）]， and pathway-related protein [adenosine monophosphate-activated protein kinase （AMPK）， phosphorylated AMPK （p-AMPK）， Yes-associated protein （YAP）， phosphorylated YAP （p-YAP）] were all determined. HepG2 human liver cancer cells were selected as subjects and divided into control group， oleic acid （OA） group， Sin 50 μmol/L group， Sin 100 μmol/L group， OA+Sin 50 μmol/L group and OA+Sin 100 μmol/L group. After 24 hours of treatment， the accumulation of lipid droplets was observed， and the expressions of pathway-related proteins were detected.RESULTS Compared to HFD group， hepatic steatosis， zengcheng@gdpu.edu.cn fibrotic lesions and lipid droplet accumulation were all alleviated in Sin groups； body weight， liver weight， liver indexes， the contents of AST， ALT， IL-1β， IL-18 in serum and TG， TC in liver tissue， the mRNA expressions of IL-1β and IL-18， and the expressions of cleaved-IL-1β and fibrosis-related proteins all decreased significantly （P＜0.01）； the protein expression of IL-1β， and the phosphorylation levels of AMPK and YAP proteins significantly increased （P＜0.01）. Compared with OA group， the lipid droplet accumulation of cells in OA+Sin groups significantly decreased， while the phosphorylation levels of AMPK and YAP proteins significantly increased （P＜0.05）. CONCLUSIONS Sin can ameliorate the inflammation， lipid deposition and fibrosis of liver tissue in mice， the mechanism of which may be associated with activating the AMPK signaling pathway and promoting YAP phosphorylation.
